Acyclic nucleotide analogues containing phosphonate groups are disclosed for example in U.S. Pat. Nos. 4,659,825, 4,808,716, 4,724,233, 5,142,051, 5,302,585, 5,208,221, 5,352,786, 5,356,886, in EP publication numbers 269,947, 481,214, 630,381, 369,409, 454,427, 468,119, 434,450, 618,214 and 398,231 and in WO 95/07920, WO 94/03467 and WO 96/33200. The teachings of these patents and publications include compounds in which a phosphonate group is linked to a defined purine or pyrimidine base, generally at the 1- or 9-position of the pyrimidine or purine bases, respectively, by way of a 2-(methoxy)propyl group, a 2-(methoxy)ethyl group, a 2-methoxy-3-hydroxypropyl group, or a 2-methoxy-3-fluoropropyl group, known respectively as PMP, PME, HPMP and FPMP purine or pyrimidine compounds. These compounds exhibit antiviral and cytostatic activity.
Daluge et al. (34th Interscience Conference on Antimicrobial Agents and Chemotherapy, Oct. 4–7, 1994) discloses carbovir derivatives in which the 6 position of the purine is substituted with cyclopropylamino, N-cyclopropyl-N-methylamino or N-aziridinyl.
Cihlar et al., “Antimicrobial Agents and Chemotherapy” 39(1): 117–124 (1995) disclose N6-aminohexyl-PMEDAP.
Holy et al., “ACS Symp. Ser.” 401:57–71 (1989) and Holy, “Kem. Ind.” 38(10):457–462 (1989) describe the antiviral activity of certain N6-substituted nucleotide analogues.
Additional phosphonate-substituted pyrimidine analogues are disclosed by Holy et al., “Collect. Czech. Chem. Commun.” 64:242–256 (1999), Eger et al., “J. Med. Chem.” 37:3057–3061 (1994), Wormstadt et al., “J. Heterocyclic Chem.” 37:1187–1191 (2000), and Franchetti et al., “Nucleosides & Nucleotides” 14(3–5):607–610 (1995). The latter three publications have a phosphonate-containing side-chain linked via a 6-N substituent of 2,4-disubstituted pyrimidine.